Modulation of calcium signalling by mitochondria.

In this review we will attempt to summarise the complex and sometimes contradictory effects that mitochondria have on different forms of calcium signalling. Mitochondria can influence Ca(2+) signalling indirectly by changing the concentration of ATP, NAD(P)H, pyruvate and reactive oxygen species - which in turn modulate components of the Ca(2+) signalling machinery i.e. buffering, release from internal stores, influx from the extracellular solution, uptake into cellular organelles and extrusion by plasma membrane Ca(2+) pumps. Mitochondria can directly influence the calcium concentration in the cytosol of the cell by importing Ca(2+) via the mitochondrial Ca(2+) uniporter or transporting Ca(2+) from the interior of the organelle into the cytosol by means of Na+/Ca(2+) or H+/Ca(2+) exchangers. Considerable progress in understanding the relationship between Ca(2+) signalling cascades and mitochondrial physiology has been accumulated over the last few years due to the development of more advanced optical techniques and electrophysiological approaches.